Clinical factors affecting acquired resistance to gefitinib in previously treated Japanese patients with advanced nonsmall cell lung cancer

Authors

  • Yoshihiko Segawa MD, PhD,

    Corresponding author
    1. Department of Medicine and Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan
    • Department of Medicine and Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, 160 Kou Minami-Umemoto-cho, Matsuyama, Ehime 791-0288, Japan
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    • Fax: (011) 81-89-999-1100.

  • Katsuyuki Hotta MD, PhD,

    1. Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital, Okayama, Japan
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  • Shigeki Umemura MD,

    1. Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital, Okayama, Japan
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  • Yoshiro Fujiwara MD,

    1. Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital, Okayama, Japan
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  • Tetsu Shinkai MD, PhD,

    1. Department of Medicine and Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan
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  • Hiroshi Ueoka MD, PhD,

    1. Department of Medicine, National Hospital Organization Sanyo Hospital, Ube, Japan
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  • Nagio Takigawa MD, PhD,

    1. Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital, Okayama, Japan
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  • Masahiro Tabata MD, PhD,

    1. Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital, Okayama, Japan
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  • Katsuyuki Kiura MD, PhD,

    1. Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital, Okayama, Japan
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  • Mitsune Tanimoto MD, PhD

    1. Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital, Okayama, Japan
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Abstract

BACKGROUND.

The risk factors for the development of acquired resistance in nonsmall cell lung cancer (NSCLC) patients responding to gefitinib are unclear. The current study assessed clinicopathologic factors affecting acquired resistance to gefitinib in previously treated patients with advanced NSCLC.

METHODS.

Between 2000 and 2004, 197 consecutive Japanese patients with advanced NSCLC underwent treatment with gefitinib. Of these patients, 56 who had continued gefitinib treatment without disease progression for at least 6 months were included in the study.

RESULTS.

At a median follow-up time of 21.6 months (range, 7.7–59.7 months), the median time to disease progression was 19.5 months, with progression-free survival rates of 68.5% at 1 year, 33.6% at 2 years, and 21.2% at 3 years. In a multivariate analysis using a Cox regression model, baseline brain metastasis was the strongest prognostic factor affecting acquired resistance to gefitinib (hazards ratio, 2.14; 95% confidence interval, 1.10- 4.17 [P = .025]). In addition, a decreased baseline hemoglobin level (P = .074) and the administration of >1 chemotherapy regimen before gefitinib treatment (P = .069) tended to be significant negative prognostic factors.

CONCLUSIONS.

In patients undergoing treatment with gefitinib, the presence of brain metastasis was strongly associated with the emergence of acquired resistance in the current series of NSCLC patients. The finding requires confirmation in a large cohort of patients with advanced NSCLC, including a non-Japanese/Asian population. Cancer 2006. © 2006 American Cancer Society.

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